Autoantibodies against type I IFNs in patients with critical influenza pneumonia
Authors: Qian Zhang, Andrés Pizzorno, Lisa Miorin, Paul Bastard, Adrian Gervais, Tom Le Voyer, Lucy Bizien, Jeremy Manry, Jérémie Rosain, Quentin Philippot, Kelian Goavec, Blandine Padey, Anastasija Cupic, Emilie Laurent, Kahina Saker, Martti Vanker, Karita Särekannu, Laurent Abel, Alessandro Aiuti, Saleh Al-Muhsen, Fahd Al-Mulla, Mark S. Anderson, Evangelos Andreakos, Andrés A. Arias, Hagit Baris Feldman, Alexandre Belot, Catherine M. Biggs, Dusan Bogunovic, Alexandre Bolze, Anastasiia Bondarenko, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Carlos D. Bustamante, Manish J. Butte, Giorgio Casari, John Christodoulou, Antonio Condino-Neto, Stefan N. Constantinescu, Megan A. Cooper, Clifton L. Dalgard, Murkesh Desai, Beth A. Drolet, Jamila El Baghdadi, Sara Espinosa-Padilla, Jacques Fellay, Carlos Flores, Paraskevi C. Fragkou, José Luis Franco, Antoine Froidure, Ioanna Evdokia Galani, Peter K. Gregersen, Bodo Grimbacher, Filomeen Haerynck, David Hagin, Rabih Halwani, Lennart Hammarström, James R. Heath, Sarah E. Henrickson, Elena W.Y. Hsieh, Eystein Husebye, Kohsuke Imai, Yuval Itan, Erich D. Jarvis, Timokratis Karamitros, Kai Kisand, Ourania Koltsida, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davood Mansouri, László Maródi, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine H. Mogensen, Tomohiro Morio, Lisa F.P. Ng, Luigi D. Notarangelo, Antonio Novelli, Giuseppe Novelli, Cliona O'Farrelly, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarström, Jean W. Pape, Rebeca Perez de Diego, David S. Perlin, Graziano Pesole, Anna M. Planas, Carolina Prando, Aurora Pujol, Lluis Quintana-Murci, Sathishkumar Ramaswamy, Vasiliki Rapti, Laurent Renia, Igor Resnick, Carlos Rodríguez-Gallego, Nikoletta Rovina, Vanessa Sancho-Shimizu, Anna Sediva, Mikko R.J. Seppänen, Mohammed Shahrooei, Anna Shcherbina, Ondrej Slaby, Andrew L. Snow, Pere Soler-Palacín, András N. Spaan, Ivan Tancevski, Stuart G. Tangye, Ahmad Abou Tayoun, Şehime Gülsün Temel, Sotirios Tsiodras, Stuart E. Turvey, K.M. Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Donald C. Vinh, Horst von Bernuth, Joost Wauters, Mayana Zatz, Pawel Zawadzki, Helen C. Su, Jean-Laurent Casanova, Pascal Morel, Pascale Richard, Brigitte Bonneaudeau, Dorothée Cannet, Pierre Gallian, Michel Jeanne, Magali Perroquin, Hind Hamzeh-Cognasse, Fabrice Cognasse, Pierre Tiberghien, Rachel Nadif, Marcel Goldberg, Anna Ozguler, Joseph Henny, Sylvie Lemonnier, Mireille Coeuret-Pellicer, Stéphane Le Got, Marie Zins, Christophe Tzourio, Stéphanie Debette, Carole Dufouil, Aïcha Soumaré, Morgane Lachaize, Nathalie Fievet, Amandine Flaig, Fernando Martin, Souad Mehlal-Sedkaoui, Jérôme Sallette, Romain Hernu, Bruno Lina, Carole Schwebel, Isabelle Wroblewski, Patrice Morand, Bertrand Souweine, Benoit Boeuf, Helene Peigue-Lafeuille, Michael Darmon, Hugues Patural, Bruno Pozzetto, Jean Pierre Quenot, Benoit Colomb, Pierre Pothier, Alexandre Belot, Maria Abad Arranz, Manuela Aguilar Guisado, Ana Escoresca Ortega, Rafaela Gallardo Ríos, Laura Merino Díaz, Maria Del Mar Muñoz Garcia, Nieves Ramírez Duque, Gloria María Romero Vázquez, Maria Jose Sánchez Cordero, Celia Salamanca Rivera, Jordi Niubó, Alexander Rombauts, Nicolás Navarrete, Laura Romero Oraa, Virginia Palomo, Tamara García-Salum, Marcela Ferres, Nicole Le Corre, Javier Sánchez-Céspedes, María Balsera-Manzanero, Jordi Carratala, Pilar Retamar-Gentil, Gabriela Abelenda-Alonso, Adoración Valiente, Pierre Tiberghien, Marie Zins, Stéphanie Debette, Isabelle Meyts, Filomeen Haerynck, Riccardo Castagnoli, Luigi D. Notarangelo, Luis I. Gonzalez-Granado, Nerea Dominguez-Pinilla, Evangelos Andreakos, Vasiliki Triantafyllia, Carlos Rodríguez-Gallego, Jordi Solé-Violán, José Juan Ruiz-Hernandez, Felipe Rodríguez de Castro, José Ferreres, Marisa Briones, Joost Wauters, Lore Vanderbeke, Simon Feys, Chen-Yen Kuo, Wei-Te Lei, Cheng-Lung Ku, Galit Tal, Amos Etzioni, Suhair Hanna, Thomas Fournet, Jean-Sebastien Casalegno, Gregory Queromes, Laurent Argaud, Etienne Javouhey, Manuel Rosa-Calatrava, Elisa Cordero, Teresa Aydillo, Rafael A. Medina, Kai Kisand, Anne Puel, Emmanuelle Jouanguy, Laurent Abel, Aurélie Cobat, Sophie Trouillet-Assant, Adolfo García-Sastre, Jean-Laurent Casanova
Journal: The Journal of Experimental Medicine (2022)

Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6–73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients’ autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients &amp;lt;70 yr of age (5.7 vs. 1.1%, P = 2.2 × 10−5), but not &amp;gt;70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10−5), especially those &amp;lt;70 yr old (OR = 139.9, P = 3.1 × 10−10). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for ∼5% of cases of life-threatening influenza pneumonia in patients &amp;lt;70 yr old.